Cesium carbonate → tert-Butyl (1-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-chloropyrimidin-2-yl)amino)phenyl)ethyl)carbamate

HRID 592402Notes

Reaction equation

HRID 592402 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)[C:5]([Cl:22])=[CH:4][N:3]=1.[NH2:23][C:24]1[CH:29]=[CH:28][C:27]([CH:30]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[CH3:31])=[CH:26][CH:25]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:19]([C:16]1([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][CH2:8][C:6]2[C:5]([Cl:22])=[CH:4][N:3]=[C:2]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([CH:30]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[CH3:31])=[CH:26][CH:25]=3)[N:7]=2)[CH2:18][CH2:17]1)(=[O:20])[NH2:21]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 22569414tert-butyl N-[1-(4-aminophenyl)ethyl]carbamateHCID 867122951-(2-(2-(2,5-Dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

Product 1

HCID 73296872tert-Butyl (1-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-chloropyrimidin-2-yl)amino)phenyl)ethyl)carbamateYield 12%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 1-(2-(2-(2,5-dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide A14 (0.080 g, 0.24 mmol), tert-butyl 1-(4-aminophenyl)ethylcarbamate (0.067 g, 0.29 mmol), Xantphos (0.0057 g, 0.010 mmol) and Cs2CO3 (0.23 g, 0.71 mmol) in 1,4-dioxane (4 mL) was bubbled with nitrogen for 10 minutes. Palladium(II) acetate (0.0010 g, 0.0045 mmol) was added and the mixture was heated at 120° C. under microwave irradiation for 25 minutes. The mixture was partitioned between water and EtOAc. The layers were separated and the aqueous was extracted with EtOAc (2 times). The combined organic extracts were washed with brine, dried (Na2SO4) and the solvent evaporated in vacuo to give the crude product. Purification by silica gel column chromatography (Combiflash Rf, 0-100% EtOAc in cyclohexane) gave the title compound 24 as a colourless oil (0.015 g, 12%). LCMS-C: rt 5.79 min; m/z 536 [M+H]+.

Workup

  1. customwas bubbled with nitrogen for 10 minutes
  2. customThe mixture was partitioned between water and EtOAc
  3. customThe layers were separated
  4. extractionthe aqueous was extracted with EtOAc (2 times)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (Na2SO4)
  7. customthe solvent evaporated in vacuo
  8. customto give the crude product
  9. customPurification by silica gel column chromatography (Combiflash Rf, 0-100% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-4e2ce840c6cf40d1b006aa3848a9f336
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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